| Background and objectiveSevere acute pancretitis(SAP) is a potentially lethal disorder with featuring sudden onset, serious conditions, high incidence of complications, and its mortality rate is up to 20%～40%, it is sure that multiple organ dysfunction syndrome (MODS) is one of main cause of death of SAP at an early stage. Despite a number of theories have been proposed to explain the pathogenesis from various aspects, there are still controversies about the mechanism. Therefore, SAP was the emphasis and unode in Gastrointestinal medicine ever since a long time ago. Studies conducted during recent years have shown that once the generous leucocyte were activated, it release Inflammatory mediators and cytokine into blood circulation. The uncontrolled release of inflammatory mediators during SAP can trigger a cascade-like reaction. These may be the pathophysiologic foundation of SAP complicating MODS. Tumor necrosis factor(TNF)αhas varied biological effect, which is produced as an inchoative mediator in the course of all the inflammatory mediator activation. Excessive expression of TNF-αduring SAP, can trigger a cascade-like reaction, which may stimulate other cytokine produced. Targeting TNF-αmay become the important target in using anti-inflammatory treatment for SAP. Infliximab is mouse/human chimeric monoclonal antibody. it has capacity to combine various TNF-α, in order to inhibit the biological activity of the plasma TNF-a to block the progression of phlegmasia,. So anti-inflammatory media therapeutics may become an new way to cure SAP. In 2001, BhaticM et al firstly proposed an new concept of anti-inflammatory media therapeutic window, which is presented between AP onset and organ dysfunction. This is a new idea to the problem of Lacking of specific operable time to cure SAP at an early stage. Previous investigation show that the time 6 h after induction of ANP model is the peak of TNF-αin ANP complicating MODS model, and thus is the anti-inflammatory media therapeutic window for ANP complicating MODS model rat. The time to cure SAP at an early stage is various, it lack of objective evidence and diagnostic and therapeutic guide. Using Infliximab, the TNF-αchimeric monoclonal antibody, to treat ANP complicating MODS rat mode have not been reported up to now. Therefore, there are two pats in our study. Part one: To explore the time-effect relationship and experimental effects of Infliximab on acute necrosis pancreatitis(ANP) complicating MODS rat model. Part two: we attempted to investigate the experimental effects of using Infliximab and Octreotide to treat ANP complicating MODS rat model. We intended to elucidate the amelioration of Infliximab and Octreotide for the first time, which were administered in anti-inflammatory media therapeutic window for treating ANP complicating MODS model rat at an early stage. So as to provide the evidence to clinical research in future.MethodPart one: To explore the time-effect relationship of Infliximab on ANP complicating MODS rats model:112 SD female rats were randomly divided into control group, ANP model group, 6 h Infliximab treated group and 9 h infliximab treated group (n=28 respectively). The Aho's method was adopted and improved. ANP animal model was induced by retrograde injection into rat's biliopancreatic duct with 4.5% of NaTc solution. In control group, the normal saline was injected into the biliopancreatic duct by the same way. Infliximab was infused 6 h and 9 h after successful modeling, were injected via caudal vein passage followed by continuous intravenous transfusion by micro-infusion pump in two treatment groups, respectively. 8 rats of each group were observed and sacrificed at 24 h after successful modeling. Serum amylase level, TNF-α. serum total bilirubin, Cr and PaO2/FiO2 of rats were determined. Tissue samples of pancreas were prepared for morphological observation under conventional light microscopy, and pathological change of pancreas was evaluated by Schmit score system. Survival rate at 24 h was observed in the rest 20 SD female rats of each group.Part tow: To investigate the experimental effects of using Infliximab and Octreotide to treat ANP complicating MODS rat model: 140 SD female rats were randomly divided into control group, ANP model group, octreotide treated group, Infliximab treated group and Infliximab plus octreotide treated group (n=28 respectively). The Aho's method was adopted and improved. ANP animal model was induced by the same way. 6 h after successful modeling, treated group was injected Infliximab or octreotide via caudal vein passage followed by continuous intravenous transfusion by micro-infusion pump, in anti-inflammatory media therapeutic window. 8 rats of each group were observed and sacrificed at 24 h after the models were induced. Serum amylase level, TNF-α. serum total bilirubin, Cr and PaO2/FiO2 of rats were determined. Tissue samples of pancreas were prepared for morphological observation under conventional light microscopy, and pathological change of pancreas was evaluated by Schmit score system. Survival rate at 24h was observed in the rest 20 SD female rats of each group.Results(1) Part one:①The contents of Serum amylase, TNF-α, serum total bilirubin and Cr of treated groups were obviously decreased (P<0.05), and the PaO2/FiO2 was significantly higher (P<0.05). Serum total bilirubin and Cr in 6 h Infliximab treated group were much significantly lower than those in 9 h Infliximab treated group (P<0.05).②Pancreatic pathology score in the treated group were significantly lower than those in the model group (P<0.05). Compared to 9 h Infliximab treated group, the pathological scores in the 6 h Infliximab treated groups were significantly lower (P<0.05).③Compared to the model group, 24 h survival rate of the treated group was elevated. while there were not significantly different (P>0.05). (2) Part two:①The contents of Serum amylase, TNF-α, serum total bilirubin and Cr of each treated groups were obviously decreased (P<0.05), and the PaO2/FiO2 was significantly higher(P<0.05). While serum total bilirubin and Cr in inflixiimab treated group and infliximab plus octreotide treated group were significantly lower than those in octreotide treated group (P<0.05). Compared to the inflixiimab treated group, the serum total bilirubin and Cr in infliximab plus octreotide treated group were much significantly lower (P<0.05).②Pancreatic pathology score in the treated group were significantly lower than those in the model group (P<0.05). Compared to the octreotide treated group, the pathological scores in the infliximab treated groups and infliximab plus octreotide treated group were significantly lower (P<0.05), while the pathological scores in the infliximab plus octreotide treated group were obviously lower than those in the infliximab treated group (P<0.05).③Compared to the model group, 24 h survival rate of the infliximab treated group, octreotide treated group and infliximab plus octreotide treated group were elevated to varying degrees. Furthermore 24 h survival rate of the infliximab plus octreotide treated group is the highest(90%), while there were not significantly different between infliximab plus octreotide treated group and model group(65%) (P>0.05).Conclusions①Infliximab can significantly lower the serum level of TNF-αand incidence rate of MODSl, and obviously ameliorate inflammation of pancreatitis in ANP complicating MODS rats mode. If the Infliximab was used at early stage, these effects may more obvious.②Inflixiimab plus octreotide, which can significantly ameliorate the organic function and pathological change of pancreas of ANP model rats, can elevate the survival rate of ANP model rats in some degree. |
PDF Full Text Request